Oblimersen Plus Doxorubicin and Docetaxel in Treating Patients With Metastatic or Locally Advanced Breast Cancer

NCT00063934 | Terminated Phase 1 Results

• 5 other identifiers: NCI-2012-028856023DM02-700P30CA016672N01CM17003
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial is studying the side effects and best dose of oblimersen when given together with doxorubicin and docetaxel and to see how well they work in treating women with metastatic or locally advanced breast cancer. Drugs used in chemotherapy, such as doxorubicin and docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of doxorubicin and docetaxel by making the tumor cells more sensitive to the drugs.

Conditions

Male Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participant With Toxicities

  From baseline until the date of first documented toxicity or date of death from any cause, whichever came first, assessed every three weeks up to 2 years and 5 months

• Number of Participants With Pathologic Complete Response (pCR)

  Pathologic complete responses (pCR), defined as no evidence of residual invasive tumor, including no residual tumor in the axillary lymph nodes, measured by microscopic evaluation of tissue specimen at time of definitive surgery (after 6 courses of neoadjuvant therapy). Neoadjuvant (preoperative) therapy administered on the first five days of every 3-week cycle. Response Evaluation Criteria in Solid Tumors (RECIST) Committee \[JNCI 92(3):205-216, 2000\]

  At time of definitive surgery (after 6 courses of neoadjuvant therapy in 3 week cycles), approximately 18 weeks

Secondary Outcomes (2)

• Clinical Imaging Responses

  After 3 and 6 courses of 21 day treatments (up to 18 weeks)

• Bcl-2 Expression in Breast Cancer Tissue

  before treatment and at 3-5 days after oblimersen treatment

Study Arms (1)

Treatment (oblimersen, doxorubicin, docetaxel)

EXPERIMENTAL

PHASE I (COMPLETED AS OF 8/16/04): Patients receive oblimersen IV continuously on days 1-6 interrupted only to administer doxorubicin IV over 15 minutes and docetaxel IV over 60 minutes on day 6. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 7-13 or pegfilgrastim SC on day 7. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. PHASE II: Patients receive doxorubicin, docetaxel, G-CSF or pegfilgrastim, and oblimersen at the MTD as in phase I. Patients with resectable tumors after 6 courses undergo surgical resection.

Biological: oblimersen sodium; Drug: doxorubicin hydrochloride; Drug: docetaxel; Biological: filgrastim; Biological: pegfilgrastim; Procedure: therapeutic conventional surgery; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

oblimersen sodium BIOLOGICAL

Given IV

Also known as: augmerosen, G3139, G3139 bcl-2 antisense oligodeoxynucleotide, Genasense

Treatment (oblimersen, doxorubicin, docetaxel)

doxorubicin hydrochloride DRUG

Given IV

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF

Treatment (oblimersen, doxorubicin, docetaxel)

docetaxel DRUG

Given IV

Also known as: RP 56976, Taxotere, TXT

Treatment (oblimersen, doxorubicin, docetaxel)

filgrastim BIOLOGICAL

Given SC

Also known as: G-CSF, Neupogen

Treatment (oblimersen, doxorubicin, docetaxel)

pegfilgrastim BIOLOGICAL

Given SC

Also known as: Filgrastim SD-01, GCSF-SD01, Neulasta, SD-01 sustained duration G-CSF

Treatment (oblimersen, doxorubicin, docetaxel)

therapeutic conventional surgery PROCEDURE

Undergo surgical resection

Treatment (oblimersen, doxorubicin, docetaxel)

pharmacological study OTHER

Optional correlative studies

Also known as: pharmacological studies

Treatment (oblimersen, doxorubicin, docetaxel)

laboratory biomarker analysis OTHER

Optional correlative studies

Treatment (oblimersen, doxorubicin, docetaxel)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PHASE I: Patients must have histologically or cytologically confirmed breast cancer
• PHASE I: To be eligible for the phase I component of this study, patients must have stage IIIB, IIIC or IV breast cancer; these include patients with T4, any N, M0; any T, N3, M0; any T, any N, M1
• PHASE I: Measurable disease is not required for patients participating in the phase I component
• PHASE I: Prior G3139, taxane or anthracycline therapy is not allowed
• PHASE I: Patients may have received up to 3 prior chemotherapy regimens for breast cancer (excluding anthracyclines and taxanes), either as adjuvant/neoadjuvant therapy or for metastatic disease
• PHASE I: Life expectancy of greater than 6 months
• PHASE I: ECOG performance status =\< 2 (Karnofsky \>= 60%)
• PHASE I: Leukocytes \>= 3,000/L
• PHASE I: Absolute neutrophil count \>= 1,500/L
• PHASE I: Platelets \>= 100,000/L
• PHASE I: Total bilirubin =\< 1.5 mg/dl
• PHASE I: ALT(SGPT) =\< 2.5 X upper limit of normal
• PHASE I: Creatinine =\< 2.0 mg/dl
• PHASE I: Normal cardiac function (LVEF \>= 45%) as documented by MUGA scan and/or echocardiogram
• PHASE I: The effects of G3139 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because anthracycline and taxanes used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

You may not qualify if:

• PHASE I: Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the phase I study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• PHASE I: Patients may not be receiving any other investigational agents
• PHASE I: Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• PHASE I: Leptomeningeal disease
• PHASE I: Symptomatic lymphangitic pulmonary metastases
• PHASE I: History of allergic reactions attributed to compounds of similar chemical or biologic composition to G3139 or other agents used in the study; patients are excluded if known hypersensitivity to drugs formulated in polysorbate 80 (Tween 80)
• PHASE I: Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• PHASE I: Patients with neuropathy grade 2 or higher
• PHASE I: Pregnant women are excluded from this study because G3139 is an oligonucleotide agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with G3139, breastfeeding should be discontinued if the mother is treated with G3139; these potential risks may also apply to other agents used in this study, such as doxorubicin and docetaxel
• PHASE II: Patients may not be receiving any other investigational agents
• PHASE II: History of allergic reactions attributed to compounds of similar chemical or biologic composition to G3139 or other agents used in the study; patients are excluded if known hypersensitivity to drugs formulated in polysorbate 80 (Tween 80)
• PHASE II: Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• PHASE II: Patients with neuropathy grade 2 or higher
• PHASE II: Pregnant women are excluded from this study because G3139 is an oligonucleotide agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with G3139, breastfeeding should be discontinued if the mother is treated with G3139; these potential risks may also apply to other agents used in this study, such as doxorubicin and docetaxel

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Breast Neoplasms, Male; Breast Neoplasms

Interventions

oblimersen; Doxorubicin; Docetaxel; Filgrastim; Granulocyte Colony-Stimulating Factor; pegfilgrastim

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Francisco Esteva, MD, PHD / Professor
• Organization: UTMDACC

Francisco.Esteva@nyumc.org

713-792-2817

Study Officials

• Francisco Esteva

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2003
• First Posted: July 9, 2003
• Study Start: May 1, 2003
• Primary Completion: February 1, 2008
• Study Completion: February 1, 2008
• Last Updated: March 5, 2019
• Results First Posted: August 16, 2012

Record last verified: 2019-02

Locations

US (1)